The goal of the project is to optimize the inherent cytotoxicity and antineoplastic activity of dolastatin 10. In phase I, the authors will develop a solid-phase synthesis of the compound by adaptation of the Evans aldol technology to the solid phase. They will then use combinatorial chemistry to apply the method to synthesizing 320 analogs and screen them for inhibition of tubulin polymerization and cytotoxicity. Any leads thus identified will be used to design subsequent focused libraries. Candidate compounds will undergo further testing in collaboration with a pharmaceutical partner. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE